Category Archives: Heart Disease

Diabetes Drug Dapagliflozin Reduced Cardiovascular Deaths and Worsening Heart Failure Even in Those Without Diabetes

 

Not dapagliflozin

The amazing thing about this research is that dapagliflozin 10 mg/day seemed to benefit patient who didn’t even have diabetes. Unfortunately, the abstract doesn’t mention how many non-diabetic patients were in the study.

Conclusion from the abstract:

Among patients with heart failure and a reduced [left ventricular] ejection fraction [under 40%], the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.

Source: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction | NEJM

Are Heart Artery Stenting and Bypass Really Necessary?

Pulmonary artery arrow is wrong

Doctors are often criticised for over-using coronary artery angioplasty/stenting and coronary artery bypass grafting.

From Stanford Medicine:

Patients with severe but stable heart disease who are treated with medications and lifestyle advice alone are no more at risk of a heart attack or death than those who undergo invasive surgical procedures, according to a large, federally-funded clinical trial led by researchers at the Stanford School of Medicine and New York University’s medical school.

The trial did show, however, that among patients with coronary artery disease who also had symptoms of angina — chest pain caused by restricted blood flow to the heart — treatment with invasive procedures, such as stents or bypass surgery, was more effective at relieving symptoms and improving quality of life.

“For patients with severe but stable heart disease who don’t want to undergo these invasive procedures, these results are very reassuring,” said David Maron, MD, clinical professor of medicine and director of preventive cardiology at the Stanford School of Medicine, and co-chair of the trial, called ISCHEMIA, for International Study of Comparative Health Effectiveness with Medical and Invasive Approaches.

***

“Based on our results, we recommend that all patients take medications proven to reduce risk of heart attack, be physically active, eat a healthy diet and quit smoking,” Maron said. “Patients without angina will not see an improvement, but those with angina of any severity will tend to have a greater, lasting improvement in quality of life if they have an invasive heart procedure. They should talk with their physicians to decide whether to undergo revascularization.”

Source: Stents, bypass surgery show no benefit in heart disease mortality rates among stable patients | News Center | Stanford Medicine

Steve Parker, M.D.

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Prevent Cardiovascular Events By Taking Hypertension Meds at Bedtime

High blood pressure is linked to heart attacksVery

This may be the most important biomedical research of 2019. Very recently I have noticed hypertension patients taking their medications at bedtime. Now I know why.

From Medscape:

Taking antihypertensive medication at bedtime led to an almost halving of cardiovascular events in a new study.

The Hygia Chronotherapy Trial is the largest ever study to investigate the effect of the time of day when people take their antihypertensive medication on the risk of cardiovascular events.

The trial randomly assigned 19,084 patients to take their medication on waking or at bedtime and followed them for an average of 6 years.Results showed that patients who took their pills at bedtime had a 45% reduction in overall cardiovascular events. This included a 56% reduction in cardiovascular death, a 34% reduction in myocardial infarction (MI), a 40% reduction in coronary revascularization [bypass surgery and angioplasty/stenting], a 42% reduction in heart failure, and a 49% reduction in stroke, all of which were statistically significant.

***

“We showed that if blood pressure is elevated during sleep then patients have increased cardiovascular risk regardless of daytime pressure, and if blood pressure during sleep is normal then cardiovascular risk is low even if the [doctor’s] office pressure is elevated,” Hermida said.

***

Results showed that during the 6.3-year median patient follow-up, 1752 participants experienced the primary cardiovascular disease (CVD) outcome (a composite of CVD death, MI, coronary revascularization, heart failure, or stroke).

Drug classes as physicians’ disposal were ARBs (angiotensin receptor blockers, calcium channel blockers, ACE inhibitors, and diuretics. Preventative effects were most pronounced for ARBs and ACE inhibitors.

Don’t change your BP medication dosing until you check with your personal physician.

Source: Bedtime Dosing of Hypertension Meds Reduces CV Events

Did you know most heart attacks occur in the morning, and those tend to be the most serious?

Steve Parker, M.D.

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Particular Diabetes Drugs May Protect Your Heart and Kidneys

 

Blood pressure control is also extremely important for protection of heart and kidneys

I’ve been reticent to tout the putative heart-protective effects of diabetes drugs in the classes called SGLT2 inhibitors and GLP-1 receptor agonists. Frankly, their supposed kidney-protective effects haven’t even been on my radar. My hesitation to report on these matters stems from:

Maybe if Big Pharma sent me a nice check….

The GLP-1 receptor agonists seem to have beneficial effects on both heart and kidney. With SGLT2 inhibitors, renal benefits may be more prominent than cardiac. Also note that any beneficial heart or renal effects may be attributable only to certain drug within the class, and not a class effect.

For what it’s worth, the American Diabetes Association recently hosted a conference on these issues. I assume the ADA endorses the report written by three experts, two of whom have received some sort of compensation from pharmaceutical companies. This doesn’t necessarily mean they are biased. Some excerpts:

Since patients with diabetes are at increased risk for CV [cardiovascular] and renal events, reducing the risk of these events is of primary interest to improve outcomes in the long-term. [Cardiovascular events usually refers to heart attacks, strokes, and death from those. Renal events would be high loss of protein through the kidneys, impaired kidney function or chronic kidney disease, or the need for dialysis.]

SGLT2 inhibitors and GLP-1 RAs have dramatically changed the treatment landscape of type 2 diabetes due to their established CV benefits, and the observed improvements in renal function seen with these classes of agents are currently undergoing intense investigation.

***

It is now apparent that both SGLT2 inhibitors and GLP-1 RAs show consistent reductions in major adverse cardiovascular events for patients with established cardiovascular (CV) disease, and both appear to have renal benefits as well.

***

The nephron is the microscopic structural and functional unit of the kidney.

Renal effects of GLP-1 receptor agonists

These drugs may exert their beneficial actions on the kidneys through their effects on lowering blood glucose and blood pressure and by reducing the levels of insulin.

For GLP-1RAs, these [studies] include ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, HARMONY with albiglutide, and REWIND with dulaglutide.

All these studies indicate that albuminuria [protein loss through urine] is reduced during treatment with GLP-1 RAs, and eGFR [estimated glomerular filtration rate, a measure of kidney function] appears to be stabilized.

These benefits are seen independently of HbA1c, weight, and blood pressure variations.

***

Heart attack is only one type of cardiovascular event

Cardiovascular effects of GLP-1 receptor agonists

Large CV outcomes trials with GLP-1 RAs have shown that these agents can reduce the risk of major adverse CV events, CV mortality, and all-cause mortality.

These CV benefits appear to be related to four distinct mechanisms:

    • Improve myocardial [heart muscle] performance in ischemic heart failure [caused by poor blood flow to heart]
    • Improve myocardial survival in ischemic heart disease
    • Ameliorate endothelial dysfunction [endothelium is the lining of arteries]
    • Decrease markers of CV risk.

***

Renal effects of SGLT2 inhibitors

  • However, many potential mechanisms have been linked to the renoprotective effects of SGLT2 inhibitors.
  • These include reduction of blood pressure, improved metabolic parameters, reduced volume overload, reduction in albuminuria, and glomerular pressure.
  • For the latter, SGLT2 inhibition appears to reduce hyperfiltration via a tubuloglomerular feedback mechanism.
  • Clinical data from CV outcomes trials have shown consistent variations in eGFR and reduction in death from renal causes with empagliflozin, canagliflozin, and dapagliflozin.
  • However, to gain more information about the renal effects of these agents, dedicated renal outcomes trials are needed to study reductions in albuminuria, changes in eGFR, number of patients reaching end-stage renal disease, need for dialysis, and deaths due to kidney failure.

***

Key Messages from the authors

Large CV outcomes trials have shown that both SGLT2 inhibitors and GLP-1 RAs are associated with significant reductions in CV events in patients with elevated CV risk.

From CV outcomes trials both classes of agents also appear to have renal benefits, although large dedicated studies are needed to establish the magnitude of this potential benefit

The mechanism of action at the basis of CV and renal benefits of SGLT2 inhibitors and GLP-1 RAs is complex, multifactorial, and still not completely understood.

I’m still skeptical but will keep an open mind.

Steve Parker, M.D.

PS: Bold emphasis above is mine.

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Diet Quality Affects Risk of Cardiovascular Disease in Post-Menopausal Diabetic Women

Not your average cave-woman

Regarding the mention of paleo diet below, I rather doubt the study at hand hand significant numbers of paleo diet followers. From the Journal of the American Heart Association:

ABSTRACT

Background Dietary patterns are associated with cardiovascular disease (CVD) risk in the general population, but diet-CVD association in populations with diabetes mellitus is limited. Our objective was to examine the association between diet quality and CVD risk in a population with type 2 diabetes mellitus.

Methods and Results

We analyzed prospective data from 5809 women with prevalent type 2 diabetes mellitus at baseline from the Women’s Health Initiative. Diet quality was defined using alternate Mediterranean, Dietary Approach to Stop Hypertension, Paleolithic, and American Diabetes Association dietary pattern scores calculated from a validated food frequency questionnaire. Multivariable Cox’s proportional hazard regression was used to analyze the risk of incident CVD. During mean 12.4 years of follow-up, 1454 (25%) incident CVD cases were documented. Women with higher alternate Mediterranean, Dietary Approach to Stop Hypertension, and American Diabetes Association dietary pattern scores had a lower risk of CVD compared with women with lower scores (Q5 v Q1) (hazard ratio [HR]aMed 0.77, 95% CI 0.65-0.93; HRDASH 0.69, 95% CI 0.58-0.83; HRADA 0.71, 95% CI 0.59-0.86). No association was observed between the Paleolithic score and CVD risk.

Conclusions

Dietary patterns that emphasize higher intake of fruits, vegetables, whole grains, nuts/seeds, legumes, a high unsaturated:saturated fat ratio, and lower intake of red and processed meats, added sugars, and sodium are associated with lower CVD risk in postmenopausal women with type 2 diabetes mellitus.

Source: Diet Quality and Cardiovascular Disease Risk in Postmenopausal Women With Type 2 Diabetes Mellitus: The Women’s Health Initiative. – PubMed – NCBI

Steve Parker, M.D.

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Red Meat Not Quite as Deadly as Imagined

From New York Times:

Public health officials for years have urged Americans to limit consumption of red meat and processed meats because of concerns that these foods are linked to heart disease, cancer and other ills.

But on Monday, in a remarkable turnabout, an international collaboration of researchers produced a series of analyses concluding that the advice, a bedrock of almost all dietary guidelines, is not backed by good scientific evidence.

Whew…What a relief! Dodged that bullet.

Click for Gina Kolata’s article.

Steve Parker, M.D.

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Tighter Blood Pressure Control Benefits Folks With Diabetes

Not bad

For decades, physicians thought a blood pressure of under 140/90 was adequate for preventing heart attacks, strokes, and premature death. Not so.

From Diabetes Self-Management:

The new study evaluated roughly 11,000 people with type 2 diabetes in 20 countries over four years, finding that those who received the blood pressure drugs perindopril and indapamide to keep their blood pressure levels at or below 130/80 had fewer heart attacks, strokes and other complications than those receiving placebo (inactive treatment). They also had a “lower overall risk of dying from any cause.”

Source: Tight Blood Pressure Control Benefits Type 2 Diabetes: Study – Diabetes Self-Management

You may think the aforementioned health benefits stem from use of perindopril and/or indapamide. It’s either that, or simply the result of BP lowering. I suspect it’s the latter while admitting that not all BP drugs are created equal. As a hospitalist in Scottsdale, AZ, I rarely run across patients taking perindopril, and only occasionally folks on indapamide. The popularity of various drugs often depends on which part of the country you’re in and the attractiveness of the drug reps visiting the prescribers. We need to be more scientific than that.

Steve Parker, M.D.

PS: Losing excess weight and exercise are two ways to lower blood pressure without the expense and side effects of drugs.

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Higher Blood Levels of Omega-3 Fatty Acids Linked to Lower Risk of Heart Failure

Salmon, a cold-water fatty fish, is a rich source of omega-3 fatty acids

Here’s the abstract from JACC: Heart Failure:

Objectives

The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial.

Background

Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear.

Methods

In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling.

Results

A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type.

Conclusions

Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)

Source: Predicting Risk for Incident Heart Failure With Omega-3 Fatty Acids | JACC: Heart Failure

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Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations

Doomed to premature death?

Ever heard of TMAO? Click that link and you’ll find that “In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported.” Uh-oh!

From European Journal of Nutrition:

Abstract

BACKGROUND:

The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes.

OBJECTIVE:

To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease.DESIGN:In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC-MS/MS.

RESULTS:

Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = - 0.34, P < 0.01).

CONCLUSIONS:

Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health.

Source: Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentr… – PubMed – NCBI

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Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. – PubMed – NCBI

I’ve probably read and blogged here about most of the individual articles that comprise this meta-analysis.

Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

There is some evidence supporting the beneficial effects of a Paleolithic Diet (PD) on cardiovascular disease risk factors. This diet advises consuming lean meat, fish, vegetables, fruits, and nuts and avoiding intake of grains, dairy products, processed foods, and added sugar and salt. This study was performed to assess the effects of a PD on cardiovascular disease risk factors including anthropometric indexes, lipid profile, blood pressure, and inflammatory markers using data from randomized controlled trials. A comprehensive search was performed in the PubMed, Scopus, ISI Web of Science, and Google Scholar databases up to August, 2018. A meta-analysis was performed using a random-effects model to estimate the pooled effect size. Meta-analysis of 8 eligible studies revealed that a PD significantly reduced body weight [weighted mean difference (WMD) = -2.17 kg; 95% CI: -3.48, -0.87 kg], waist circumference (WMD = -2.90 cm; 95% CI: -4.51, -1.28 cm), body mass index (in kg/m2) (WMD = -1.15; 95% CI: -1.68, -0.62), body fat percentage (WMD = -1.38%; 95% CI: -2.08%, -0.67%), systolic (WMD = -4.24 mm Hg; 95% CI: -7.11, -1.38 mm Hg) and diastolic (WMD = -2.95 mm Hg; 95% CI: -4.72, -1.18 mm Hg) blood pressure, and circulating concentrations of total cholesterol (WMD = -0.22 mg/dL; 95% CI: -0.42, -0.03 mg/dL), TGs (WMD = -0.23 mg/dL; 95% CI: -0.46, -0.01 mg/dL), LDL cholesterol (WMD = -0.13 mg/dL; 95% CI: -0.25, -0.01 mg/dL), and C-reactive protein (CRP) (WMD = -0.41 mg/L; 95% CI: -0.81, -0.008 mg/L) and also significantly increased HDL cholesterol (WMD = 0.05 mg/dL; 95% CI: 0.005, 0.10 mg/dL). However, sensitivity analysis revealed that the overall effects of a PD on lipid profile, blood pressure, and circulating CRP concentrations were significantly influenced by removing some studies, hence the results must be interpreted with caution. Although the present meta-analysis revealed that a PD has favorable effects on cardiovascular disease risk factors, the evidence is not conclusive and more well-designed trials are still needed.

Advances in Nutrition. 2019 Apr 30. pii: nmz007. doi: 10.1093/advances/nmz007. [Epub ahead of print]. Authors are Ghaedi E., Mohammadi M, Mohammadi H, Ramezani-Jolfaie N, Malekzadeh J, Hosseinzadeh M, Salehi-Abargouei A.

Source: Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. – PubMed – NCBI